The spatial extent of retinal and choroidal damage will be probed with noninvasive, quantitative mapping of visual function and structure. We will continue to study the distinction between aging changes and disease processes, particularly for age-related macular degeneration (AMD). The goal is to determine why patients lose vision and to identify factors that are amenable to treatment to save vision. The long-term goals address three main thrusts of the NEI National Plan, 1999-2003: to provide early diagnosis, explore the pathophysiological heterogeneity of AMD, and develop effective strategies for screening for eye disease. Aging is an important cross-cutting issue. This study includes important co-factors that increase with age: atherosclerotic disease, glaucoma, and Type II diabetes. Further, our longitudinal data indicate that epiretinal membranes, considered an inner retinal abnormality, are an important clinical entity in our AMD patients. We plan studies with clinical relevance to reach this goal, including both on-going cross-sectional and longitudinal studies.We will use advanced imaging methods that are unique, rapid, and resistant to stray light. To investigate photoreceptor function in living humans, we will develop new methods that will measure the photopigment within cones and rods in patients or regions of the retina not amenable to study previously.To investigate the damage to support cells beneath the photoreceptors, the retinal pigment epithelial cells, we will use techniques primarily with near infrared light that is comfortable and virtually invisible. These are visible even through moderate cataract and hemorrhage. We will combine imaging techniques with novel methods of image processing. We will investigate the mechanisms of vision loss in several new groups, some of which exacerbate factors that may be important in vision loss, or change the retinal microenvironment in disease. We will include groups in our studies that are at high risk for vision loss, and minority groups, who have been excluded in many other studies but represent clinical management problems. Specifically, the effects of aging will be compared with age-related macular degeneration alone and in the presence of disease commonly found in this age group: atherosclerotic cardiovascular disease, glaucoma, and type Il diabetes. The cardiovascular study includes measuring before and after rehabilitation. The spatial extent and distribution of drusen, new vessel membranes, retinal vascular changes, and undetected edema in these groups is information that can used for evaluating possible preventative measures, determining the focal effects of treatment, estimating prognosis.